Nearly Complete Genome Sequence of a Novel Phlebovirus-Like Virus Detected in a Human Plasma Sample by High-Throughput Sequencing.

Here, we report a novel phlebovirus-like virus sequence detected in a plasma sample from a febrile adult patient collected in the United Republic of Tanzania in 2014. A nearly complete RNA sequence was generated by high-throughput sequencing on a HiSeq 2500 instrument and further confirmed after repeating the analysis, starting from the initial sample

Implications from dimensionless parameter scaling experiments

The dimensionless parameter scaling approach is increasingly useful for predicting future tokamak performance and guiding theoretical models of energy transport. Experiments to determine the {rho}* (gyroradius normalized to plasma size) scaling have been carried out in many regimes. The electron {rho}* scaling is always ``gyro-Bohm``, while the ion {rho}* scaling varied with regime. The ion variation is correlated with both density scale length (L mode, H mode) and current profile. The ion {rho}* scaling in the low-q, H-mode regime is gyro-Bohm, which is the most favorable confinement scaling observed. New experiments in {beta} scaling and collisionality scaling have been carried out in low-q discharges in both L mode and H mode. In L mode, global analysis shows that there is a slightly unfavorable {beta} dependence ({beta}{sup {minus}0.1}) and no {nu}* dependence. In H-mode, global analysis finds a weak {beta} dependence ({beta}{sup 0.1}) and an unfavorable dependence on {nu}*. The lack of significant {beta} scaling spans the range of {beta}{sub N} from 0.25 to 2.0. The very small {beta} dependence in L mode and H mode is in contradiction with the standard global scaling relations. This contradiction in H mode may be indicative of the impact on the H-mode database of low-n tearing instabilities which are observed at slightly higher {beta}{sub N} in the {beta} scaling experiments. The measured {beta} and {nu}* scalings explain the weak density dependence observed in engineering parameter scans. It also points to the power of the dimensionless parameter approach, since it is possible to obtain a definitive size scaling from experiments on a single tokamak

The spectra and energies of classical double radio lobes

We compare two temporal properties of classical double radio sources: i) radiative lifetimes of synchrotron-emitting particles and ii) dynamical source ages. We discuss how these can be quite discrepant from one another, rendering use of the traditional spectral ageing method inappropriate: we contend that spectral ages give meaningful estimates of dynamical ages only when these ages are << 10^7 years. In juxtaposing the fleeting radiative lifetimes with source ages which are significantly longer, a refinement of the paradigm for radio source evolution is required. The changing spectra along lobes are explained, not predominantly by synchrotron ageing but, by gentle gradients in a magnetic field mediated by a low-gamma matrix which illuminates an energy-distribution of particles, controlled largely by classical synchrotron loss in the high magnetic field of the hotspot. The energy in the particles is an order of magnitude higher than that inferred from the minimum-energy estimate, implying that the jet-power is of the same order as the accretion luminosity produced by the quasar central engine. This refined paradigm points to a resolution of the findings of Rudnick et al (1994) and Katz-Stone & Rudnick (1994) that both the Jaffe-Perola and Kardashev-Pacholczyk model spectra are invariably poor descriptions of the curved spectral shape of lobe emission, and indeed that for Cygnus A all regions of the lobes are characterised by a `universal spectrum'. [abridged]Comment: LaTeX, 4 figures. To appear in A

Characteristics and outcomes of patients treated with apremilast in the real world: results from the APPRECIATE study

Background APPRECIATE is a multinational, observational, retrospective, cross‐sectional study in patients treated for psoriasis with apremilast, an oral phosphodiesterase 4 inhibitor. Objectives To describe the characteristics of patients with psoriasis treated with apremilast in the clinical setting, to evaluate real‐world outcomes of psoriasis treatment with apremilast and to better understand the perspectives of patients and physicians on treatment outcomes. Methods In six European countries, patients with chronic plaque psoriasis treated in clinical practice who could be contacted 6 (±1) months after apremilast initiation were enrolled. Patient characteristics, Dermatology Life Quality Index (DLQI) and Psoriasis Area and Severity Index (PASI) were obtained from medical records when available. Outcomes were evaluated using patient/physician questionnaires. Results In 480 patients at treatment initiation, mean [median; 95% confidence interval (CI)] PASI and DLQI scores were 12.5 (10.7; 11.6–13.4) and 13.4 (13.0; 11.4–14.2), respectively. At 6 (±1) months, 72.3% of patients (n = 347) continued apremilast treatment [discontinuations: lack of efficacy (13.5%), safety (11.7%), other (2.5%)]. In patients continuing treatment, 48.6% achieved a ≥75% reduction in PASI score; mean (95% CI) DLQI score was 5.7 (4.5–6.9), and mean (SD) Patient Benefit Index score was 2.8 (1.2). Physicians perceived clinical improvement in 75.6% of patients. Physicians’ perspective on overall success of apremilast in meeting expectations correlated with patients’ perception of treatment benefit (r = 0.691). Most commonly reported adverse events (>5% of patients) were diarrhoea, nausea and headache. Conclusions Patients in APPRECIATE reported high disease burden despite more moderate skin involvement than those who enrolled in clinical trials of apremilast. Findings from APPRECIATE demonstrate the real‐world value of apremilast for psoriasis treatment, as 7 of 10 patients continued therapy and showed notable improvement in disease severity and quality of life 6 (±1) months after apremilast initiation

E119D Neuraminidase Mutation Conferring Pan-Resistance to Neuraminidase Inhibitors in an A(H1N1)pdm09 Isolate From a Stem-Cell Transplant Recipient

Background. An influenza A(H1N1)pdm09 infection was diagnosed in a hematopoietic stem cell transplant recipient during conditioning regimen. He was treated with oral oseltamivir, later combined with intravenous zanamivir. The H275Y neuraminidase (NA) mutation was first detected, and an E119D NA mutation was identified during zanamivir therapy. Methods. Recombinant wild-type (WT) E119D and E119D/H275Y A(H1N1)pdm09 NA variants were generated by reverse genetics. Susceptibility to NA inhibitors (NAIs) was evaluated with a fluorometric assay using the 2′-(4-methylumbelliferyl)-α-d-N-acetylneuraminic acid (MUNANA) substrate. Susceptibility to favipiravir (T-705) was assessed using plaque reduction assays. The NA affinity and velocity values were determined with NA enzymatic studies. Results. We identified an influenza A(H1N1)pdm09 E119D mutant that exhibited a marked increase in the 50% inhibitory concentrations against all tested NAIs (827-, 25-, 286-, and 702-fold for zanamivir, oseltamivir, peramivir, and laninamivir, respectively). The double E119D/H275Y mutation further increased oseltamivir and peramivir 50% inhibitory concentrations by 790- and >5000-fold, respectively, compared with the WT. The mutant viruses remained susceptible to favipiravir. The NA affinity and velocity values of the E119D variant decreased by 8.1-fold and 4.5-fold, respectively, compared with the WT. Conclusions. The actual emergence of a single NA mutation conferring pan-NAI resistance in the clinical setting reinforces the pressing need to develop new anti-influenza strategie

CD8+ cytolytic T cell clones derived against the Plasmodium yoelii circumsporozoite protein protect against malaria

Immunization of BALB/c mice with radiation-attenuated Plasmodium yoelii sporozoites induces cytotoxic T lymphocytes (CTL) specific for an epitope located within the amino acid sequence 277-288 of the P. yoelii circumsporozoite (CS) protein. Several CD8+ CTL clones were derived from the spleen cells of sporozoite-immunized mice, all displaying an apparently identical epitope specificity. All the clones induced high levels of cytolysis in vitro upon exposure to peptide-incubated MHC-compatible target cells. The adoptive transfer of two of these clones conferred complete protection against sporozoite challenge to naive mice. This protection is species and stage specific. Using P. yoelii specific ribosomal RNA probes to monitor the in vivo effects of the CTL clones, we found that their target was the intrahepatocytic stage of the parasite. The protective clones completely inhibited the development of the liver stages of P. yoelii. Some CTL clones were only partially inhibitory in vivo, while others failed completely to alter liver stage development and to confer any detectable degree of protection. The elucidation of the effector mechanism of this CTL mediated protection against rodent malaria should facilitate the design of an effective malaria vaccine. From a broader perspective this model may provide further insight into the mechanism(s) of CTL mediated killing of intracellular non-viral pathogens in general